title: Synthesis of novel benzo-fused heteroaryl derivatives as Ca²⁺/calmodulin-dependent protein kinase II inhibitors.
abstract: Based on the structure activity relationship of 2-(4-phenoxybenzoyl)-5-hydroxyindole (1), a novel structural class of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibitors were synthesized. We show in this study that the acidic proton at the N(1)-position of the indole moiety is not essential for CaMKII inhibitory activity. Among the synthesized compounds, we found the benzofuran and benzothiazole derivative as promising scaffolds for the developement of potent CaMKII inhibitors. In particular, compounds 8 and 14 inhibited CaMKII with IC₅₀ values of 24 nM and 32 nM, respectively.
authors.affiliation: Research Division, Dainippon Sumitomo Pharma Co., Ltd.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Komiya
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Asano
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Koike
authors.forename: Erina
authors.initials: E
authors.lastname: Koga
authors.forename: Junetsu
authors.initials: J
authors.lastname: Igarashi
authors.forename: Shogo
authors.initials: S
authors.lastname: Nakatani
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Isobe
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001572:Benzofurans; D052160:Benzothiazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; C026785:5-hydroxyindole; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C005465:benzothiazole; C105430:benzofuran